Treatment of DAA-Experienced Patients with Chronic Hepatitis C
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Purpose of Review
The development of interferon-free direct-acting antiviral (DAA) regimens for the treatment of chronic hepatitis C (HCV) has significantly improved rates of sustained virologic response (SVR), shortened treatment duration, and improved drug tolerability across genotypes. While SVR rates now exceed 95% among treatment-naïve patients, there are a growing number of patients who have experienced DAA treatment failure and represent an emerging clinical challenge. This review discusses recent data on sofosbuvir/velpatasvir/voxilaprevir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir for the treatment of DAA-experienced patients, as well as updated American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines.
Data from phase 3 randomized clinical trials show that retreatment of DAA failures is successful in > 90% of patients using the above three regimens. The preferred retreatment regimen is dependent on HCV genotype, possible drug-drug interactions, prior treatment experience, and host factors such as the presence of cirrhosis and renal failure. Sofosbuvir/velpatasvir is a reasonable option for DAA-experienced genotype 1b and genotype 2 patients, but has been shown to be inferior to sofosbuvir/velpatasvir/voxilaprevir in genotype 1a and genotype 3 patients. Glecaprevir/pibrentasvir is a very attractive option for treatment of DAA-experienced genotype 1 and 2 patients, but it is not approved for treatment of DAA-experienced patients with genotype 3, and data is lacking to support its use in DAA treatment-experienced patients with genotypes 4–6.
The potency and high barrier to resistance of newer DAA regimens create an opportunity to cure most people with chronic hepatitis C, regardless of prior treatment failures. It is now possible to consider elimination of hepatitis C; the remaining barriers are the cost of therapy and access to care.
KeywordsHepatitis C Retreatment Directly acting antivirals Chronic
Compliance with Ethical Standards
Conflict of Interest
Maria A. Corcorran declares no conflicts of interest.
John D. Scott reports personal fees from Novartis, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Wyles D, Mangia A, Cheng W, Shafran S, Schwabe C, Ouyang W, et al. Long-term persistence of HCV NS5A resistance associated substitutions after treatment with the HCV NS5A inhibitor, ledipasvir, without sofosbuvir. Antivir Ther. 2017;Google Scholar
- 4.•• AASLD/IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. https://www.hcvguidelines.org. Consensus guidelines on the retreatment of hepatitis C, with a review of recent pivotal studies.
- 5.Kim, A. 2017 IDWeek abstract 943 Management of first line HCV treatment failures, Oct 6, 2017. San Diego, CA.Google Scholar
- 9.Brown A, et al. Adherence to pangenotypic glecaprevir/pibrentasvir treatment and SVR12 in HCV-infected patients: an integrated analysis of the phase 2/3 clinical trial program. Abstract 198. AASLD 2017, Washington.Google Scholar
- 10.Terrault NA, Zeuzem S, di Bisceglie AM, Lim JK, Pockros PJ, Frazier LM, et al. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated of sustained virologic response. Gastroenterology. 2016;151(6):1131–40.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Spach, DH, Kim HN. Treatment of HCV genotype 1. Hepatitis C Online Updated November 15, 2017. https://www.hepatitisc.uw.edu/browse/all/core-concepts.
- 15.• Poordad F, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 66(2):389–97. Phase 3 study of glecaprevir and pibrentasvir in prior DAA failures. Google Scholar
- 16.Poordad F, et al. MAGELLAN-1, part 2: glecaprevir and pibrentasvir for 12 or 16 weeks in patients with chronic hepatitis C virus genotype 1 or 4 and prior direct-acting antiviral treatment failure. J Hepatol. 66(1):S83–4.Google Scholar
- 17.Zeuzem S, Feld J, Wang S. ENDURANCE-1: efficacy and safety of 8- versus 12-week treatment with ABT-493/ABT-530 in patients with chronic HCV genotype 1 infection [Abstract 253]. In 67th Annual Meeting of the American Association for the Study of Liver diseases, November 11–15. 2016.Google Scholar
- 18.Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicenter phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.CrossRefPubMedGoogle Scholar
- 21.Spach DH, Kim HN. Treatment of HCV genotype 2. Hepatitis C Online. 2016. https://www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-2/core-concept/all.
- 22.Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2017;16:417–26. https://doi.org/10.1016/j.cgh.2017.09.027. CrossRefPubMedGoogle Scholar
- 24.• Wyles D, et al. Hepatology. 2017; https://doi.org/10.1002/hep.29541. A smaller study that only examined patients who had failed sofosbuvir.
- 25.Hepatitis C Online. Hepatitis C treatments https://www.hepatitisc.uw.edu/page/treatment/drugs/glecaprevir-pibrentasvir/drug-summary.